IN VIVO OPTICAL DIAGNOSIS OF ORAL MALIGNANCY IN HUMAN SUBJECTS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：早期发现癌症及其可治愈的先兆仍然是确保患者生存和生活质量的最好方法。尽管在治疗方面取得了重大进展，但口腔癌仍导致美国每年有1万人死亡，这主要是由于大多数口腔病变的发现较晚。具体目的：利用体内非侵入性光学技术的组合，测试一种多模式方法来对受试者口腔癌前病变和恶性肿瘤进行非侵入性诊断。方法：对30例健康、发育不良和/或恶性口腔组织进行活体光学相干断层扫描(OCT)和光学多谱勒断层扫描(ODT)，在常规活检前在特定的标记部位定位上皮、上皮下和血管的变化。体外多波长多光子(MPM)和二次谐波(SHG)荧光技术提供了表面和亚表面组织结构的平行数据，特别是胶原的存在和结构，细胞的存在和血管系统。图像的诊断由2名盲目、预标准化的调查人员进行，所有模式的标准评分从0到6。制作组织病理切片，病理评分为0~6分。方差分析技术将成像诊断与组织病理学进行了比较。应用ROC曲线和Kappa统计量建立OCT/ODT+MPM/SHG诊断能力的敏感性和特异性的95%置信限。结果：成像数据重复性好，准确度高。异型增生和恶性肿瘤相关的结构和血管改变在组织深度为2 mm时清晰可见。与常规方法相比，其敏感性(OCT/ODT：72-89%；OCT+MPM/SHG：76-90%)和特异性(OCT：68-84%；OCT+MPM/SHG：74-88%)均较好。结论：OCT/ODT和MPM/SHG是口腔异型增生和口腔恶性肿瘤的无创性体内诊断方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim: Using a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy in human subjects. Methods: In 30 patients with healthy, dysplastic, and/or malignant oral tissues, in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change in specific, marked sites prior to routine biopsy. Ex vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. Histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Dysplasia- and malignancy-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 72-89%; OCT+MPM/SHG: 76-90%) and specificity (OCT alone: 68-84%;OCT+MPM/SHG: 74-88%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy.